Tyrosinase and Ocular Diseases: Some Novel thoughts on the Molecular basis of Oculocutaneous Albinism type 1
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Tyrosinase and Ocular Diseases: Some Novel thoughts on the
Molecular basis of Oculocutaneous Albinism type 1
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| Creator |
Ray, Kunal
Chaki, Moumita Sengupta, Mainak |
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| Subject |
Molecular & Human Genetics
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| Description |
Tyrosinase (TYR) is a multifunctional copper-containing glycoenzyme (�80 kDa), which plays a key role in the rate-limiting steps of
the melanin biosynthetic pathway. This membrane-bound protein, possibly evolved by the fusion of two different copper-binding
proteins, is mainly expressed in epidermal, ocular and follicular melanocytes. In the melanocytes, TYR functions as an integrated unit
with other TYR-related proteins (TYRP1, TYRP2), lysosome-associated membrane protein 1 (LAMP1) and melanocyte-stimulating
hormone receptors; thus forming a melanogenic complex. Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause
oculocutaneous albinism type 1 (OCA1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance. In
addition, TYR can act as a modifier locus for primary congenital glaucoma (PCG) and it also contributes significantly in the eye
developmental process. Expression of TYR during neuroblast division helps in later pathfinding by retinal ganglion cells from retina to
the dorsal lateral geniculate nucleus. However, mutation screening of TYR is complicated by the presence of a pseudogene–TYR like
segment (TYRL, 11p11.2, MIM 191270), sharing �98% sequence identity with the 30 region of TYR. Thus, in absence of a full-proof
strategy, any nucleotide variants identified in the 30 region of TYR could actually be present in TYRL. Interestingly, despite extensive
search, the second TYR mutation in 15% of the OCA1 cases remains unidentified. Several possible locations of these ‘‘uncharacterized
mutations’’ (UCMs) have been speculated so far. Based on the structure of TYR gene, its sequence context and some experimental
evidences, we propose two additional possibilities, which on further investigations might shed light on the molecular basis of UCMs in
TYR of OCA1 patients; (i) partial deletion of the exons 4 and 5 region of TYR that is homologous with TYRL and (ii) variations in the
polymorphic GA complex repeat located between distal and proximal elements of the human TYR promoter that can modulate the
expression of the gene leading to disease pathogenesis.
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| Date |
2007
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1153/1/PROGRESS_IN_RETINAL_AND_EYE_RESEARCH_26_(4)_323%2D358;2007[68].pdf
Ray, Kunal and Chaki, Moumita and Sengupta, Mainak (2007) Tyrosinase and Ocular Diseases: Some Novel thoughts on the Molecular basis of Oculocutaneous Albinism type 1. Progress in Retinal and Eye Research, 26 (4). pp. 323-358. |
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| Relation |
http://dx.doi.org/10.1016/j.preteyeres.2007.01.001
http://www.eprints.iicb.res.in/1153/ |
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